• 제목/요약/키워드: Candidate gene approach

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Immunotherapeutic Approach for Better Management of Cancer - Role of IL-18

  • Kuppala, Manohar Babu;Syed, Sunayana Begum;Bandaru, Srinivas;Varre, Sreedevi;Akka, Jyothy;Mundulru, Hema Prasad
    • Asian Pacific Journal of Cancer Prevention
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    • 제13권11호
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    • pp.5353-5361
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    • 2012
  • Interleukin-18 (IL-18) is an immune-stimulatory cytokine with antitumor activity in preclinical models. It plays pivotal roles in linking inflammatory immune responses and tumor progression and is a useful candidate in gene therapy of lymphoma or lymphoid leukemia. A phase I study of recombinant human IL-18 (rhIL-18) in patients with advanced cancer concluded that rhIL-18 can be safely given in biologically active doses to patients with advanced cancer. Some viruses can induce the secretion of IL-18 for immune evasion. The individual cytokine activity might be potentiated or inhibited by combinations of cytokines. Here we focus on combinational effects of cytokines with IL-18 in cancer progression. IL-18 is an important non-invasive marker suspected of contributing to metastasis. Serum IL-18 may a useful biological marker as independent prognostic factor of survival. In this review we cover roles of IL-18 in immune evasion, metastasis and angiogenesis, applications for chemotherapy and prognostic or diagnostic significance.

An Information-Intensive Approach to the Molecular Pharmacology of Cancer

  • John N. Weinstein;Timothy G. Myers;Patrick M. O′Connor;Stephen H. Friend;Albert J. Fornace Jr;Kurt W. Kohn;Tito Fojo;Susan E. Bates;Lawrence V. Rubinstein;N. Leigh Anderson;John K. Buolamwini;Wiliam W. van Osdol;Anne P. Monks;Dominic A. Scudiero;Edward A. Sausville;Daniel W. Zaharevitz;Barry Bunow;Vellarkda N. Viswanadhan;Georage S. Johnson;Robert E. Wittes;Kennety D. Paull
    • 한국생물정보학회:학술대회논문집
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    • 한국생물정보시스템생물학회 2001년도 제2회 생물정보학 국제심포지엄
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    • pp.139-149
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    • 2001
  • Since 1990, the National Cancer Institute(NCI) has screened more than 60.000 compounds against a panel of 60 human cancer cell lines. The 50-percent growth-inhibitory concentration (GI$_{50}$) values encode unexpectedly rich, detailed information on mechanisms of drug action and drug resistance. Each compound's pattern is like a fingerprint, essentially unique among the many billions of distinguishable possibilities. These activity patterns are being used in conjunction with molecular structural features of the tested agents to explore the NCI's database of more than 460, 000 compounds, and they are providing insight into potential target molecules and modulators of activity in the 60 cell lines. For example, the information is being used to search for candidate anticancer drugs that are not dependent on intact p53 suppressor gene function for their activity. It remains to be seen how effective this information-intensive strategy will be at generating new clinically active agents.s.

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Some Universal Characteristics of Intertidal Bacterial Diversity as Revealed by 16S rRNA Gene-Based PCR Clone Analysis

  • Shuang, J.L.;Liu, C.H.;An, S.Q.;Xing, Y.;Zheng, G.Q.;Shen, Y.F.
    • Journal of Microbiology and Biotechnology
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    • 제16권12호
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    • pp.1882-1889
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    • 2006
  • A 16S rDNA clone library was generated to investigate the bacterial diversity in intertidal sediment from the coast of the Yellow Sea, P. R. China. A total of 102 clones were sequenced and grouped into 73 OTUs using a phylogenetic approach. The sequenced clones fell into 11 bacterial lineages: Proteobacteria, Bacteroidetes, Planctomycetes, Chloroflexi, Acidobacteria, Actinobacteria, Firmicutes, Spirochaetes, and candidate divisions of BRCl, OP3, and OP1l. Based on a phylogenetic analysis of these bacteria, together with the ten most closely related sequences deposited in the GenBank, it was concluded that intertidal bacteria are most likely derived from marine bacteria with a remarkable diversity, and some are particularly abundant in intertidal sediment.

Identification of Novel Binding Partners for Caspase-6 Using a Proteomic Approach

  • Jung, Ju Yeon;Lee, Su Rim;Kim, Sunhong;Chi, Seung Wook;Bae, Kwang-Hee;Park, Byoung Chul;Kim, Jeong-Hoon;Park, Sung Goo
    • Journal of Microbiology and Biotechnology
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    • 제24권5호
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    • pp.714-718
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    • 2014
  • Apoptosis is the process of programmed cell death executed by specific proteases, the caspases, which mediate the cleavage of various vital proteins. Elucidating the consequences of this endoproteolytic cleavage is crucial to understanding cell death and other related biological processes. Although a number of possible roles for caspase-6 have been proposed, the identities and functions of proteins that interact with caspase-6 remain uncertain. In this study, we established a cell line expressing tandem affinity purification (TAP)-tagged caspase- 6 and then used LC-MS/MS proteomic analysis to analyze the caspase-6 interactome. Eight candidate caspase-6-interacting proteins were identified. Of these, five proteins (hnRNP-M, DHX38, ASPP2, MTA2, and UACA) were subsequently examined by co-immunoprecipitation for interactions with caspase-6. Thus, we identified two novel members of the caspase-6 interactome: hnRNP-M and MTA2.

Screening of Differential Promoter Hypermethylated Genes in Primary Oral Squamous Cell Carcinoma

  • Khor, Goot Heah;Froemming, Gabrielle Ruth Anisah;Zain, Rosnah Binti;Abraham, Mannil Thomas;Thong, Kwai Lin
    • Asian Pacific Journal of Cancer Prevention
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    • 제15권20호
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    • pp.8957-8961
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    • 2014
  • Background: Promoter hypermethylation leads to altered gene functions and may result in malignant cellular transformation. Thus, identification of biomarkers for hypermethylated genes could be useful for diagnosis, prognosis, and therapeutic treatment of oral squamous cell carcinoma (OSCC). Objectives: To screen hypermethylated genes with a microarray approach and to validate selected hypermethylated genes with the methylation-specific polymerase chain reaction (MSPCR). Materials and Methods: Genome-wide analysis of normal oral mucosa and OSCC tissues was conducted using the Illumina methylation microarray. The specified differential genes were selected and hypermethylation status was further verified with an independent cohort sample of OSCC samples. Candidate genes were screened using microarray assay and run by MSPCR analysis. Results: TP73, PIK3R5, and CELSR3 demonstrated high percentages of differential hypermethylation status. Conclusions: Our microarray screening and MSPCR approaches revealed that the signature candidates of differentially hypermethylated genes may possibly become potential biomarkers which would be useful for diagnostic, prognostic and therapeutic targets of OSCC in the near future.

Study of Modern Human Evolution via Comparative Analysis with the Neanderthal Genome

  • Ahmed, Musaddeque;Liang, Ping
    • Genomics & Informatics
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    • 제11권4호
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    • pp.230-238
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    • 2013
  • Many other human species appeared in evolution in the last 6 million years that have not been able to survive to modern times and are broadly known as archaic humans, as opposed to the extant modern humans. It has always been considered fascinating to compare the modern human genome with that of archaic humans to identify modern human-specific sequence variants and figure out those that made modern humans different from their predecessors or cousin species. Neanderthals are the latest humans to become extinct, and many factors made them the best representatives of archaic humans. Even though a number of comparisons have been made sporadically between Neanderthals and modern humans, mostly following a candidate gene approach, the major breakthrough took place with the sequencing of the Neanderthal genome. The initial genome-wide comparison, based on the first draft of the Neanderthal genome, has generated some interesting inferences regarding variations in functional elements that are not shared by the two species and the debated admixture question. However, there are certain other genetic elements that were not included or included at a smaller scale in those studies, and they should be compared comprehensively to better understand the molecular make-up of modern humans and their phenotypic characteristics. Besides briefly discussing the important outcomes of the comparative analyses made so far between modern humans and Neanderthals, we propose that future comparative studies may include retrotransposons, pseudogenes, and conserved non-coding regions, all of which might have played significant roles during the evolution of modern humans.

Culturing Simpler and Bacterial Wilt Suppressive Microbial Communities from Tomato Rhizosphere

  • Roy, Nazish;Choi, Kihyuck;Khan, Raees;Lee, Seon-Woo
    • The Plant Pathology Journal
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    • 제35권4호
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    • pp.362-371
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    • 2019
  • Plant phenotype is affected by a community of associated microorganisms which requires dissection of the functional fraction. In this study, we aimed to culture the functionally active fraction of an upland soil microbiome, which can suppress tomato bacterial wilt. The microbiome fraction (MF) from the rhizosphere of Hawaii 7996 treated with an upland soil or forest soil MF was successively cultured in a designed modified M9 (MM9) medium partially mimicking the nutrient composition of tomato root exudates. Bacterial cells were harvested to amplify V3 and V4 regions of 16S rRNA gene for QIIME based sequence analysis and were also treated to Hawaii 7996 prior to Ralstonia solanacearum inoculation. The disease progress indicated that the upland MM9 $1^{st}$ transfer suppressed the bacterial wilt. Community analysis revealed that species richness was declined by successive cultivation of the MF. The upland MM9 $1^{st}$ transfer harbored population of phylum Proteobacteria (98.12%), Bacteriodetes (0.69%), Firmicutes (0.51%), Actinobacteria (0.08%), unidentified (0.54%), Cyanobacteria (0.01%), FBP (0.001%), OD1 (0.001%), Acidobacteria (0.005%). The family Enterobacteriaceae of Proteobacteria was the dominant member (86.76%) of the total population of which genus Enterobacter composed 86.76% making it a potential candidate to suppress bacterial wilt. The results suggest that this mixed culture approach is feasible to harvest microorganisms which may function as biocontrol agents.

Gene Discovery Analysis from Mouse Embryonic Stem Cells Based on Time Course Microarray Data

  • Suh, Young Ju;Cho, Sun A;Shim, Jung Hee;Yook, Yeon Joo;Yoo, Kyung Hyun;Kim, Jung Hee;Park, Eun Young;Noh, Ji Yeun;Lee, Seong Ho;Yang, Moon Hee;Jeong, Hyo Seok;Park, Jong Hoon
    • Molecules and Cells
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    • 제26권4호
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    • pp.338-343
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    • 2008
  • An embryonic stem cell is a powerful tool for investigation of early development in vitro. The study of embryonic stem cell mediated neuronal differentiation allows for improved understanding of the mechanisms involved in embryonic neuronal development. We investigated expression profile changes using time course cDNA microarray to identify clues for the signaling network of neuronal differentiation. For the short time course microarray data, pattern analysis based on the quadratic regression method is an effective approach for identification and classification of a variety of expressed genes that have biological relevance. We studied the expression patterns, at each of 5 stages, after neuronal induction at the mRNA level of embryonic stem cells using the quadratic regression method for pattern analysis. As a result, a total of 316 genes (3.1%) including 166 (1.7%) informative genes in 8 possible expression patterns were identified by pattern analysis. Among the selected genes associated with neurological system, all three genes showing linearly increasing pattern over time, and one gene showing decreasing pattern over time, were verified by RT-PCR. Therefore, an increase in gene expression over time, in a linear pattern, may be associated with embryonic development. The genes: Tcfap2c, Ttr, Wnt3a, Btg2 and Foxk1 detected by pattern analysis, and verified by RT-PCR simultaneously, may be candidate markers associated with the development of the nervous system. Our study shows that pattern analysis, using the quadratic regression method, is very useful for investigation of time course cDNA microarray data. The pattern analysis used in this study has biological significance for the study of embryonic stem cells.

Cr(VI) Resistance and Removal by Indigenous Bacteria Isolated from Chromium-Contaminated Soil

  • Long, Dongyan;Tang, Xianjin;Cai, Kuan;Chen, Guangcun;Shen, Chaofeng;Shi, Jiyan;Chen, Linggui;Chen, Yingxu
    • Journal of Microbiology and Biotechnology
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    • 제23권8호
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    • pp.1123-1132
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    • 2013
  • The removal of toxic Cr(VI) by microorganisms is a promising approach for Cr(VI) pollution remediation. In the present study, four indigenous bacteria, named LY1, LY2, LY6, and LY7, were isolated from Cr(VI)-contaminated soil. Among the four Cr(VI)-resistant isolates, strain LY6 displayed the highest Cr(VI)-removing ability, with 100 mg/l Cr(VI) being completely removed within 144 h. It could effectively remove Cr(VI) over a wide pH range from 5.5 to 9.5, with the optimal pH of 8.5. The amount of Cr(VI) removed increased with initial Cr(VI) concentration. Data from the time-course analysis of Cr(VI) removal by strain LY6 followed first-order kinetics. Based on the 16S rRNA gene sequence, strain LY6 was identified as Pseudochrobactrum asaccharolyticum, a species that had never been reported for Cr(VI) removal before. Transmission electron microscopy and energy dispersive X-ray spectroscopy analysis further confirmed that strain LY6 could accumulate chromium within the cell while conducting Cr(VI) removal. The results suggested that the indigenous bacterial strain LY6 would be a new candidate for potential application in Cr(VI) pollution bioremediation.

Evaluation of genetic differentiation and search for candidate genes for reproductive traits in pigs

  • Elena Romanets;Siroj Bakoev;Timofey Romanets;Maria Kolosova;Anatoly Kolosov;Faridun Bakoev;Olga Tretiakova;Alexander Usatov;Lyubov Getmantseva
    • Animal Bioscience
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    • 제37권5호
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    • pp.832-838
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    • 2024
  • Objective: The use of molecular genetic methods in pig breeding can significantly increase the efficiency of breeding and breeding work. We applied the Fst (fixsacion index) method, the main focus of the work was on the search for common options related to the number of born piglets and the weight of born piglets, since today the urgent task is to prevent a decrease in the weight of piglets at birth while maintaining high fertility of sows. Methods: One approach is to scan the genome, followed by an assessment of Fst and identification of selectively selected regions. We chose Large White sows (n = 237) with the same conditions of keeping and feeding. The data were collected from the sows across three farrowing. For genotyping, we used GeneSeek GGP Porcine HD Genomic Profiler v1, which included 68,516 single nucleotide polymorphisms evenly distributed with an average spacing of 25 kb (Illumina Inc, San Diego, CA, USA). Results: Based on the results of the Fst analysis, 724 variants representing selection signals for the signs BALWT, BALWT1, NBA, and TNB (weight of piglets born alive, average weight of the 1st piglets born alive, total number born alive, total number born). At the same time, 18 common variants have been identified that are potential markers for both the number of piglets at birth and the weight of piglets at birth, which is extremely important for breeding work to improve reproductive characteristics in sows. Conclusion: Our work resulted in identification of variants associated with the reproductive characteristics of pigs. Moreover, we identified, variants which are potential markers for both the number of piglets at birth and the weight of piglets at birth, which is extremely important for breeding work to improve reproductive performance in sows.